Statins or the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA) inhibitors have been the mainstay of treatment of dyslipidemia. They are often the first-line drugs to reduce the risk of atherosclerotic cardiovascular disease (ASCVD). Statin-associated muscle symptoms are the most common reasons for discontinuation of statin treatment. Fear of exacerbation of these symptoms is often the reason why statin users are hesitant or avoid exercise.

Debunking this myth, a new study of 100 participants from The Netherlands, published online April 3, 2023 in the Journal of the American College of Cardiology, has shown no worsening of muscle pain, muscle injury or fatigue among statin users following moderate-intensity exercise, such as walking.^1,2

To compare the effect of moderate-intensity exercise on muscle injury in statin users, researchers selected 35 symptomatic (muscle cramps, pain and/or weakness), 34 asymptomatic statin users and 31 non-statin users were selected as controls. All the study participants were instructed to walk for 30, 40, or 50 km daily for 4 successive days at the annual “4Day Marches” held in Nijmegen, The Netherlands proclaimed to be “The walk of the world”, at a self-determined pace.

Biomarkers of muscle injury (assessed by levels of lactate dehydrogenase, myoglobin, creatine kinase, cardiac troponin I and N-terminal pro-brain natriuretic peptide), muscle performance and reported muscle symptoms were evaluated at the start of the study and also after exercise. Baseline leukocyte coenzyme Q10 (CoQ10) was measured. Patients with diabetes or a hereditary skeletal muscle defect or any other disease known to cause muscle symptoms were not included in the study. Hypothyroid or hyperthyroid patients were also excluded from the study group. Body mass index, waist circumference, vitamin D3 status and physical activity levels were comparable between the three groups at baseline

All the muscle injury markers were found to be elevated following moderate-intensity exercise in all groups. But the levels were comparable between the groups at baseline and also after exercise.  Muscle pain scores were found to be higher among the symptomatic statin users at baseline. Muscle pain and fatigue scores increased in all groups; this increase, however, was comparable between all the three groups. A similar trend was observed for fatigue scores. Handgrip strength and muscle peak force, to evaluate muscle performance, showed similar decreases in all groups. Decrease in muscle oxygen consumption after exercise was similar in the three groups.

Muscle relaxation time after exercise was seen to increase more in the symptomatic statin user group vs the control group. The CoQ 10 levels were also similar among the asymptomatic participants (2.1 nmol/U), symptomatic participants (2.3 nmol/U) and the controls (2.1 nmol/U).  

Statin users complained of more muscle pain and fatigue at the start of the study. But after exercise, all the three groups had similar increase in muscle symptoms demonstrating that use of statins did not aggravate either muscle symptoms or muscle injury after moderate exercise. Deficiency of CoQ10 has been associated with statin‐associated muscle symptoms and exercise intolerance. But no correlation was observed between levels of CoQ 10 and markers of muscle injury, muscle symptoms or fatigue resistance in the present study. However, the authors have cautioned that the CoQ10 levels were measured in leukocytes, which they note is “not the gold standard”.³

Hence, patients taking statins can safely engage in moderate-intensity exercise without being apprehensive about symptom exacerbation and remain physically active to ward off their cardiovascular risk.

References

1. Allard NAE, et al. Prolonged moderate-intensity exercise does not increase muscle injury markers in symptomatic or asymptomatic statin users. J Am Coll Cardiol. 2023 Apr 11;81(14):1353-1364. doi: 10.1016/j.jacc.2023.01.043.
2. ACC News story. Available at: https://www.acc.org/latest-in-cardiology/articles/2023/04/03/17/00/moderate-exercise-safe-for-people-with-muscle-pain-from-statins. April 3, 2023. Accessed on April 13, 2023.
3. Michael ORiordan. Moderate-intensity exercise possible for patients with statin side effects. Available at: https://www.tctmd.com/news/moderate-intensity-exercise-possible-patients-statin-side-effects. April 3, 2023. Accessed on April 13, 2023.